WO2021000569A1 - 一种用于大面积显微成像的数字病理扫描仪 - Google Patents

一种用于大面积显微成像的数字病理扫描仪 Download PDF

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Publication number
WO2021000569A1
WO2021000569A1 PCT/CN2020/071393 CN2020071393W WO2021000569A1 WO 2021000569 A1 WO2021000569 A1 WO 2021000569A1 CN 2020071393 W CN2020071393 W CN 2020071393W WO 2021000569 A1 WO2021000569 A1 WO 2021000569A1
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WO
WIPO (PCT)
Prior art keywords
row
digital image
digital
image sensors
fov
Prior art date
Application number
PCT/CN2020/071393
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English (en)
French (fr)
Chinese (zh)
Inventor
唐玉豪
于綦悦
何俊峰
吴庆军
韦建飞
邓建
刘亚鸿
周雄兵
王阳
Original Assignee
达科为（深圳）医疗设备有限公司
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Application filed by 达科为（深圳）医疗设备有限公司 filed Critical 达科为（深圳）医疗设备有限公司
Priority to EP20835151.0A priority Critical patent/EP3816698B1/de
Priority to US17/266,172 priority patent/US11422354B2/en
Publication of WO2021000569A1 publication Critical patent/WO2021000569A1/zh

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    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B21/00—Microscopes
    • G02B21/36—Microscopes arranged for photographic purposes or projection purposes or digital imaging or video purposes including associated control and data processing arrangements
    • G02B21/365—Control or image processing arrangements for digital or video microscopes
    • G02B21/367—Control or image processing arrangements for digital or video microscopes providing an output produced by processing a plurality of individual source images, e.g. image tiling, montage, composite images, depth sectioning, image comparison
    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B21/00—Microscopes
    • G02B21/36—Microscopes arranged for photographic purposes or projection purposes or digital imaging or video purposes including associated control and data processing arrangements
    • G02B21/362—Mechanical details, e.g. mountings for the camera or image sensor, housings
    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B21/00—Microscopes
    • G02B21/0004—Microscopes specially adapted for specific applications
    • G02B21/002—Scanning microscopes
    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B21/00—Microscopes
    • G02B21/02—Objectives
    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B21/00—Microscopes
    • G02B21/24—Base structure
    • G02B21/241—Devices for focusing
    • G02B21/244—Devices for focusing using image analysis techniques
    • G—PHYSICS
    • G02—OPTICS
    • G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
    • G02B21/00—Microscopes
    • G02B21/36—Microscopes arranged for photographic purposes or projection purposes or digital imaging or video purposes including associated control and data processing arrangements
    • H—ELECTRICITY
    • H04—ELECTRIC COMMUNICATION TECHNIQUE
    • H04N—PICTORIAL COMMUNICATION, e.g. TELEVISION
    • H04N23/00—Cameras or camera modules comprising electronic image sensors; Control thereof
    • H04N23/45—Cameras or camera modules comprising electronic image sensors; Control thereof for generating image signals from two or more image sensors being of different type or operating in different modes, e.g. with a CMOS sensor for moving images in combination with a charge-coupled device [CCD] for still images

Definitions

  • the invention relates to the technical field of digital pathology imaging, in particular to a digital pathology scanner used for large-area microscopic imaging.
  • Digital pathology refers to the application of computers and networks to the field of pathology. It is a technology that combines modern digital systems with traditional optical amplification devices. It mainly uses digital pathology scanners to scan sliced tissues.
  • the conventional digital pathology scanner adopts a microscopic optical system composed of a microscope objective lens and a digital camera to perform horizontal and vertical linear scanning of the sliced tissue.
  • This scanning method results in a small scanning area and a long time, which greatly reduces the user experience of the digital pathology scanner and cannot realize the application value of digital pathology in actual clinical diagnosis.
  • the present invention provides a digital pathology scanner for large-area microscopic imaging.
  • the main purpose of the present invention is to solve the problem that the existing digital pathology scanner scans a slice of tissue in a single scan area, which causes a long time-consuming process. technical problem.
  • the present invention mainly provides the following technical solutions:
  • the embodiment of the present invention provides a digital image sensor assembly, including a plurality of microscope objective lenses and a plurality of digital image sensors; the number of the microscope objective lens and the digital image sensor is equal, and the number of the microscope objective lens and the digital image sensor are equal, and they keep relative fixed;
  • the digital image sensors are arranged in sequence to form a sensor array
  • the images formed by the digital image sensors are arranged in the second direction in sequence without intervals; the first direction is perpendicular to the second direction.
  • the present invention is further configured as follows: the sensor array has N parallel and spaced rows along the first direction, and N is an integer greater than or equal to 2;
  • the offset of the N1th row is the distance of FoV; when N2 is equal to N, the N2th row protrudes from the N1th row along the second direction by the distance of FoV; FoV is the image formed by the digital image sensor in the second direction Size.
  • the present invention is further configured as: the number of digital image sensors in each row is more than two, and they are arranged sequentially along the second direction;
  • the distance between two adjacent digital image sensors in each row in the second direction is equal, and both are r1.
  • N is the smallest integer greater than or equal to (W+r)/FoV;
  • W is the size of the digital sensor along the second direction; r is the smallest distance that can be achieved in the second direction by the processing technology of two adjacent digital image sensors in the same row.
  • the present invention is further configured as follows: the distance between two adjacent rows in the first direction is r2, and r2 is the minimum distance that can be achieved in the first direction by the processing technology of the digital image sensor in the two adjacent rows.
  • the digital pathology scanner for large-area microscopic imaging of the present invention has at least the following beneficial effects:
  • each microscopic objective lens and digital image sensor are arranged in an array, and each microscopic objective lens and the digital image sensor are kept relatively fixed in a one-to-one correspondence.
  • the array moves in a first direction, such as a longitudinal direction
  • the images formed by each digital image sensor are arranged in a second direction such as the horizontal direction without intervals, so that the microscopic images can be photographed and stitched in parallel, which can greatly increase the speed of pathological scanning and improve the use of digital pathological scanners.
  • Experience has truly realized the application value of digital pathology.
  • Fig. 1 is an array arrangement of a combination of a microscope objective lens and a digital image sensor according to an embodiment of the present invention
  • Fig. 2 is an array arrangement of a combination of a microscope objective lens and a digital image sensor according to another embodiment of the present invention
  • Fig. 3 is an array arrangement of digital image sensors according to an embodiment of the present invention.
  • Fig. 4 is an array arrangement of digital image sensors provided by another embodiment of the present invention.
  • the directional indication is only used to explain that it is in a specific posture (as shown in the drawings). If the specific posture changes, the relative positional relationship, movement, etc. of the components below will also change the directional indication accordingly.
  • an embodiment of the present invention proposes a digital pathology scanner for large-area microscopic imaging, which includes multiple microscope objective lenses 1 and multiple digital image sensors 2.
  • the number of the microscope objective lens 1 and the digital image sensor 2 are equal, and they are kept relatively fixed in one-to-one correspondence.
  • the external light is irradiated on the digital image sensor 2 through the microscope objective lens 1, and the digital image sensor 2 processes the received light and converts it into electrical signal output for digital imaging.
  • the above-mentioned digital image sensors 2 are arranged in sequence to form a sensor array.
  • the images formed by the digital image sensors 2 are arranged in the second direction in sequence without intervals; the first direction is perpendicular to the second direction.
  • the first direction may be the X direction in FIGS. 1 and 2
  • the second direction may be the Y direction in FIGS. 1 and 2.
  • the microscopic objective lenses 1 corresponding to the digital image sensors 2 are also arranged in an array. Because each microscopic objective lens 1 and the digital image sensor 2 are kept relatively fixed in a one-to-one correspondence, the objective lens array formed by the microscopic objective lens 1 will move synchronously when the sensor array moves.
  • the sensor array and the microscope objective lens array move together in the first direction, such as moving along the X direction in Figures 1 and 2, each microscope objective lens 1 in the microscope objective lens array scans each part of the tissue slice at the same time, so that The images formed by the digital image sensors 2 are sequentially arranged in a second direction, such as the Y direction, without intervals.
  • the microscopic objective lens array and the digital image sensor array scan the tissue slice in one direction
  • the microscopic images can be photographed and stitched in parallel, which is more than 20 times faster than the conventional method in the prior art , which greatly improves the user experience of digital pathology scanners and truly realizes the application value of digital pathology.
  • each microscopic objective lens 1 corresponds to the digital image sensor 2 one-to-one
  • the arrangement and method of the array formed by each microscopic objective lens 1 and the sensor array are consistent.
  • Those skilled in the art can infer the arrangement of the microscope objective lens array based on the arrangement of the sensor array.
  • the digital image sensors 2 in the sensor array may have a variety of different arrangements, for example, they may be arranged in an inclined line or in a zigzag arrangement.
  • the sensor array may have N parallel rows arranged at intervals along the first direction.
  • N is an integer greater than or equal to 2.
  • two adjacent rows are respectively the N1th row and the N2th row along the first direction.
  • N2 N1+1, N1 is an integer greater than or equal to 1.
  • the N2th row is offset from the N1th row by a distance of FoV along the second direction. FoV is the size of the image formed by the digital image sensor 2 in the second direction.
  • the sensor array has a first row, a second row, a third row, a fourth row, a fifth row, and a sixth row in the X direction.
  • the second row is offset from the first row by a distance of FoV in the Y direction.
  • the third row is offset from the second row by FoV in the Y direction.
  • the fourth row is offset from the third row by FoV in the Y direction.
  • the fifth row is offset from the fourth row by FoV in the Y direction.
  • Row 6 is offset from row 5 by FoV in the Y direction.
  • the sensor array has N parallel and spaced rows along the first direction.
  • N is an integer greater than or equal to 3.
  • the number of digital image sensors 2 located in the two outermost rows in the sensor array is equal, and they are all M1.
  • two adjacent rows are respectively the N1th row and the N2th row along the first direction.
  • the N2th row is offset from the N1th row in the second direction by a distance of FoV; when N2 is equal to N, the N2th row protrudes from the N1th row in the second direction by a distance of FoV; FoV is the size of the image formed by the digital image sensor 2 in the second direction.
  • the sensor array has a first row, a second row, a third row, a fourth row, a fifth row, and a sixth row in the X direction.
  • the number of digital image sensors 2 is the same in the first row and the sixth row, and the numbers of the digital image sensors 2 in the fourth row to the fifth row are the same.
  • the number of digital image sensors 2 in the first row is one more than the number of digital image sensors 2 in the second row.
  • the second row is offset from the first row by a distance of FoV in the Y direction.
  • the third row is offset from the second row by FoV in the Y direction.
  • the fourth row is offset from the third row by FoV in the Y direction.
  • the fifth row is offset from the fourth row by FoV in the Y direction.
  • the 6th row protrudes FoV in the Y direction relative to the 5th row.
  • the number of the digital image sensors 2 in each row may be more than two, and they may be sequentially arranged along the second direction.
  • the distance between two adjacent digital image sensors 2 in each row in the second direction is equal, and both are r1. This can make the structure of the sensor array more compact and smaller.
  • the corresponding arrangement parameters of the aforementioned sensor array can be obtained using the following formula.
  • N is the smallest integer greater than or equal to (W+r)/FoV.
  • r1 N*FoV-W.
  • W is the size of the digital image sensor 2 along the second direction; r is the smallest distance that can be achieved in the second direction by the processing technology of two adjacent digital image sensors 2 in the same row.
  • r2 is the smallest distance that can be achieved in the first direction by the processing technology of the digital image sensor 2 in the two adjacent rows.
  • the arrangement parameters calculated by the above formula can make the sensor array have the smallest arrangement structure.
  • the volume of the sensor array arranged by the above method is small, and each digital image in the sensor array
  • the effective utilization of sensor 2 is relatively high.
  • FoV can be obtained through image measurement of the digital image sensor 2.
  • W can be obtained by measuring the size of the digital image sensor.
  • r can be obtained through process evaluation.
  • the following is a specific example of the sensor array adopting a zigzag arrangement.
  • a digital image sensor array the dimensions of the digital image sensor 2 are as follows: the width W is 5.18 mm, and the height H is 5.4 mm.
  • the imaging range FoV is 1.0 mm.
  • the digital image sensor 2 binding and packaging process stipulates that the minimum horizontal distance r is 0.8 mm, and the minimum vertical distance r2 is 0.82 mm.
  • the specific number of digital image sensors 2 in each row can be determined according to actual conditions, and the details are not repeated here.
  • a digital image sensor array the dimensions of the digital image sensor 2 are as follows: the width W is 8.5 mm, and the height H is 8.5 mm.
  • the imaging range FoV is 1.0 mm.
  • the digital image sensor 2 binding and packaging process stipulates that the minimum horizontal distance r is 0.3 mm, and the minimum vertical distance r2 is 0.3 mm.
  • the specific number of digital image sensors 2 in each row can be determined according to actual conditions, and the details are not repeated here.
  • the microscopic objective lens 1 and the digital image sensor 2 of the present invention are arranged in an array, and the arrangement of the two is the same, for example, an inclined inline arrangement or a zigzag arrangement can be adopted. Both the microscope objective lens array and the digital image sensor array remain relatively fixed. When the array scans the tissue slice linearly in one direction, it can shoot and stitch microscopic images in parallel, which is more than 20 times faster than the conventional method, and the volume is reduced, the cost is reduced, which greatly improves the user of the digital pathology scanner The user experience truly realizes the application value of digital pathology.

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  • Physics & Mathematics (AREA)
  • Engineering & Computer Science (AREA)
  • General Physics & Mathematics (AREA)
  • Optics & Photonics (AREA)
  • Chemical & Material Sciences (AREA)
  • Analytical Chemistry (AREA)
  • Multimedia (AREA)
  • Computer Vision & Pattern Recognition (AREA)
  • Signal Processing (AREA)
  • Human Computer Interaction (AREA)
  • Image Input (AREA)
  • Microscoopes, Condenser (AREA)
  • Studio Devices (AREA)
PCT/CN2020/071393 2019-07-01 2020-01-10 一种用于大面积显微成像的数字病理扫描仪 WO2021000569A1 (zh)

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Application Number Priority Date Filing Date Title
EP20835151.0A EP3816698B1 (de) 2019-07-01 2020-01-10 Digitaler pathologischer scanner zur grossflächigen mikroskopischen abbildung
US17/266,172 US11422354B2 (en) 2019-07-01 2020-01-10 Digital pathology scanner for large-area microscopic imaging

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CN201910586372.XA CN110244445B (zh) 2019-07-01 2019-07-01 一种用于大面积显微成像的数字病理扫描仪
CN201910586372.X 2019-07-01

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US20210311293A1 (en) 2021-10-07
CN110244445A (zh) 2019-09-17
EP3816698C0 (de) 2023-11-08
CN110244445B (zh) 2024-08-30
EP3816698A4 (de) 2021-11-17
EP3816698A1 (de) 2021-05-05
US11422354B2 (en) 2022-08-23
EP3816698B1 (de) 2023-11-08

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